Transdermal Delivery of Interferon Alpha-2B using Microporation and Iontophoresis in Hairless Rats

Badkar, Advait; Smith, Alan M.; Eppstein, Jonathan A.; Banga, Ajay K.

doi:10.1007/s11095-007-9308-2

Cited by 84 publications

(41 citation statements)

References 25 publications

(28 reference statements)

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“…The effects we measured were probably irreversible in vitro, but should be reversible in vivo over the timescale of normal skin healing mechanisms. Indeed, previous in vivo studies suggest that the effects of short, high temperature exposures are reversible (Badkar et al, 2007;Lee et al, 2002;Sintov et al, 2003).…”

Section: Effect Of Heat On Skin Permeabilitymentioning

confidence: 99%

“…However, applications of short, high temperature heating of skin envision the heating as a pretreatment (Badkar et al, 2007;Birchall et al, 2006;Bramson et al, 2003;Fang et al, 2004;Fujiwara et al, 2005;Lee et al, 2001;Levin et al, 2005;Sintov et al, 2003). Thus, these methods are directly relevant to transdermal drug delivery applications.…”

Section: Effect Of Heat On Skin Permeabilitymentioning

confidence: 99%

“…This approach has been used in a number of previous studies (Badkar et al, 2007;Birchall et al, 2006;Bramson et al, 2003;Lee et al, 2001;Nelson et al, 1991;Sintov et al, 2003) and is the subject of commercial development by a few companies (e.g., Altea Therapeutics, TransPharma Medical). Despite this progress in the field, there remains uncertainty about the mechanisms by which these short, hot pulses increase skin permeability.…”

Section: Applications To Transdermal Drug Deliverymentioning

confidence: 99%

“…Rapidly heating the skin surface is hypothesized to locally ablate the stratum corneum without significantly heating, or damaging, deeper tissues. Activation of an array of microheaters on the skin surface has been shown to increase insulin and vaccine delivery (Badkar et al, 2007;Bramson et al, 2003). Radio-frequency heating of skin has also been shown to increase delivery of small molecule drugs, human growth hormone, and DNA (Birchall et al, 2006;Levin et al, 2005;Sintov et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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The effect of heat on skin permeability

Park¹,

Lee

Kim

et al. 2008

International Journal of Pharmaceutics

110

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a b s t r a c tAlthough the effects of long exposure ( 1 s) to moderate temperatures (≤100 • C) have been well characterized, recent studies suggest that shorter exposure (<1 s) to higher temperatures (>100 • C) can dramatically increase skin permeability. Previous studies suggest that by keeping exposures short, thermal damage can be localized to the stratum corneum without damaging deeper tissue. Initial clinical trials have progressed to Phase II (see http://clinicaltrials.gov), which indicates the procedure can be safe. Because the effect of heating under these conditions has received little systematic or mechanistic study, we heated full-thickness skin, epidermis and stratum corneum samples from human and porcine cadavers to temperatures ranging from 100 to 315 • C for times ranging from 100 ms to 5 s. Tissue samples were analyzed using skin permeability measurements, differential scanning calorimetry, thermomechanical analysis, thermal gravimetric analysis, brightfield and confocal microscopy, and histology. Skin permeability was shown to be a very strong function of temperature and a less strong function of the duration of heating. At optimal conditions used in this study, transdermal delivery of calcein was increased up to 760-fold by rapidly heating the skin at high temperature. More specifically, skin permeability was increased (I) by a few fold after heating to approximately 100-150 • C, (II) by one to two orders of magnitude after heating to approximately 150-250 • C and (III) by three orders of magnitude after heating above 300 • C. These permeability changes were attributed to (I) disordering of stratum corneum lipid structure, (II) disruption of stratum corneum keratin network structure and (III) decomposition and vaporization of keratin to create micron-scale holes in the stratum corneum, respectively. We conclude that heating the skin with short, high temperature pulses can increase skin permeability by orders of magnitude due to structural disruption and removal of stratum corneum.

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Section: Effect Of Heat On Skin Permeabilitymentioning

confidence: 99%

Section: Effect Of Heat On Skin Permeabilitymentioning

confidence: 99%

Section: Applications To Transdermal Drug Deliverymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The effect of heat on skin permeability

Park¹,

Lee

Kim

et al. 2008

International Journal of Pharmaceutics

110

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“…Application of iontophoresis on pretreated skin further pushes the charged molecules down these pathways and into the deeper layers of the skin. This combination approach has been reported to increase drug delivery by several fold (29,(86)(87)(88). For example, Daniplestim, a peptide with a molecular weight of 13 kDa was shown to have higher delivery levels after the combination treatment as compared with iontophoresis alone (87).…”

Section: Combination Strategiesmentioning

confidence: 99%

Transdermal Delivery of Proteins

2011

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Abstract. Transdermal delivery of peptides and proteins avoids the disadvantages associated with the invasive parenteral route of administration and other alternative routes such as the pulmonary and nasal routes. Since proteins have a large size and are hydrophilic in nature, they cannot permeate passively across the skin due to the stratum corneum which allows the transport of only small lipophilic drug molecules. Enhancement techniques such as chemical enhancers, iontophoresis, microneedles, electroporation, sonophoresis, thermal ablation, laser ablation, radiofrequency ablation and noninvasive jet injectors aid in the delivery of proteins by overcoming the skin barrier in different ways. In this review, these enhancement techniques that can enable the transdermal delivery of proteins are discussed, including a discussion of mechanisms, sterility requirements, and commercial development of products. Combination of enhancement techniques may result in a synergistic effect allowing increased protein delivery and these are also discussed.

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Transdermal Microfluidic Continuous Monitoring Systems

Cunningham

2009

In Vivo Glucose Sensing

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Transdermal Delivery of Interferon Alpha-2B using Microporation and Iontophoresis in Hairless Rats

Abstract: In vivo delivery of IFNalpha2b was demonstrated through micropores created in the outer layer of the skin. Iontophoresis enhanced delivery through microporated skin in hairless rats.

Cited by 84 publications

References 25 publications

The effect of heat on skin permeability

The effect of heat on skin permeability

Transdermal Delivery of Proteins

Transdermal Microfluidic Continuous Monitoring Systems

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